The long-term goal of this program is the therapeutic exploitation of the reduced cysteine biosynthetic capability of malignant lymphoid cells as compared to their normal counterparts (In Vivo, 9, 303 (1974); Cell 7, 41(1976)), J. Biol. Chem., 252, 7184 (1977). This will be attempted by isolating and characterizing enzymes that are capable of degrading cysteine and cystine and that have suitable kinetic and pharmacologic properties for use in vivo. Enzymes which have the ability to create a rapid in vivo cysteine depletion will be evaluated for their antineoplastic efficacy. Studies also will be initiated to optimize enzyme therapy by combination with low molecular weight inhibitors of host cysteine biosynthesis and chemical modification of enzyme antigenicity and clearance properties.